AB0102 POTENTIAL BIOMARKERS TO PREDICT TNF INHIBITORS OUTCOME IN PSORIATIC ARTHRITIS
Authors: A. Makos, J. H. Kuiper, R. Amarasena, O. Kehoe
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Psoriatic Arthritis (PsA) is a chronic immune-mediated inflammatory disease characterized by axial and peripheral arthritis, dactylitis, nail changes and most of the time, is associated with psoriasis. Patients are initially treated with conventional synthetic Disease-Modifying Anti-Rheumatic Drugs (csDMARDs), but if they do not respond to these, they are treated with biologics, particularly TNF inhibitors (TNFi) which are common first-line biologics. However, about 40% of patients do not or only partially respond to TNFi. Blood biomarkers predicting response to TNFi would allow patients to be treated earlier with a more appropriate drug [1]. <h3>Objectives</h3> We studied pro- and anti-inflammatory cytokines and adaptive immune cells that could be used as biomarkers for TNFi outcome. Predicting responses to TNFi will help clinicians to choose a more appropriate treatment for patients. <h3>Methods</h3> Blood from patients with PsA (n = 8) was analysed before starting TNFi and compared with blood from patients with rheumatoid arthritis (RA) (n = 8). PsA patients were characterised as 'psoriasis positive' and 'psoriasis negative'. Patients were followed at 3 and 6 months after treatment (n = 6). Leukocytes were isolated with Lymphoprep and their phenotype was characterised by CD45, CD3, CD4, CXCR3, CCR6, HLA-DR, CD38, CD25 and CD127. Levels of 12 cytokines in plasma were measured using a cytokine kit (MACSPlex Cytokine 12 Kit, human, Miltenyi Biotec Ltd, UK). Clinical data from patients were collected to determine treatment outcome. <h3>Results</h3> Mean level of TNFα was higher in our RA patients (6.2 pg/ml) compared to our PsA patients (4.6 pg/ml). Initial analysis of clinical data suggested that our PsA patients without psoriasis (n = 2) responded better to TNFi than those with active psoriasis (n = 4) at 3 months and 6 months after treatment, with a clear reduction in the number of tender joints ('psoriasis positive': 6.65 vs 1.67; 'psoriasis negative': 11.5 vs 0.67) and swollen joints ('psoriasis positive': 2 vs 0.67; 'psoriasis negative': 3.50 vs 0). The mean proportion of activated Th17 cells was higher in our patients with active psoriasis (5.1% of Th17 cells) than those without psoriasis (3.6% of Th17 cells). The mean level of IL-12 and INFγ was higher in the 'psoriasis positive' group (respectively 129.2 pg/ml and 266.1 pg/ml) than the 'psoriasis negative' group (respectively 52.7 pg/ml and 115 pg/ml). <h3>Conclusion</h3> We hypothesize that PsA patients have a lower level of TNFα because of other pro-inflammatory cytokines potentially involved in the inflammatory process. IL-12 can induce IFNγ production by Th1 cells and is involved in the IL12/IL23 axis in psoriasis pathogenesis. IFNγ can induce Th1 and Th17 cells expansion through myeloid dendritic cells activation. In PsA, the high levels of IL-12 and IFNγ involved in psoriasis pathogenesis might be one of the reasons for a poor response to treatment, but larger sample sizes are needed to find a biomarker that could be used routinely by clinicians, and to determine if the same biomarker can also be used for other types of arthritis such as rheumatoid arthritis. <h3>Reference</h3> [1]Makos A et al., Inflammopharmacol (2022) doi: 10.1007/s10787-022-01092-x <h3>Acknowledgements</h3> We would like to acknowledge the Rheumatology clinical team and research nurses at the RAJH Orthopaedic Hospital, and PsA and RA patients for participating in the study. <h3>Disclosure of Interests</h3> None Declared.